Variant rs255690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001999.4(FBN2):c.2863+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,577,716 control chromosomes in the GnomAD database, including 84,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5731 hom., cov: 33)

Exomes 𝑓: 0.32 ( 79072 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.271

Variant links:

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

FBN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-128349932-C-A is Benign according to our data. Variant chr5-128349932-C-A is described in ClinVar as [Benign]. Clinvar id is 258514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.2863+23G>T		intron_variant		ENST00000262464.9	NP_001990.2	P35556-1
FBN2	XM_017009228.3 linkuse as main transcript	c.2710+23G>T		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.2863+23G>T		intron_variant		1	NM_001999.4	ENSP00000262464.4		P35556-1
FBN2	ENST00000508989.5 linkuse as main transcript	c.2764+23G>T		intron_variant		2		ENSP00000425596.1		D6RJI3

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38085

AN:

152080

Hom.:

5728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.280

AC:

70163

AN:

250474

Hom.:

10842

AF XY:

0.281

AC XY:

38016

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.324

AC:

462250

AN:

1425518

Hom.:

79072

Cov.:

AF XY:

0.322

AC XY:

229060

AN XY:

711380

show subpopulations

Gnomad4 AFR exome

AF:

0.0968

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.250

AC:

38092

AN:

152198

Hom.:

5731

Cov.:

AF XY:

0.240

AC XY:

17891

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.322

Hom.:

8422

Bravo

AF:

0.254

Asia WGS

AF:

0.158

AC:

552

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over